It is extensively accepted that, in advanced cases of DDH, which frequently combined with severe degeneration and osteoarthritis, severe pain sensation and dysfunction in hip joint would always be the primary complaint
[31, 32]. Current studies have focused mainly on the members of tachykinin family as well as its roles in the pain creation of osteoarthritis. Besides, the relationship between neuropeptides and cytokines in joint fluid and serum of patients with OA or RA were also studied
[33, 34]. Moreover, BN/GRP and SP in both serum and synovial fluid were found correlated with inflammation index such as CRP and ESR in patients with RA in hip joint
. These observations indicated that, as a typical nerve tachykinin, SP as well as some of the other neuropeptides might associated with inflammation and degeneration in hip joint and may also have some relationships with the occurrence of pain sensation.
In our study, the level of nerve tachykinin SP is up-regulated in both serum and synovial tissue from patients with DDH&OA compared to that in patients with DDH. Through serum test, we also observed some positive relationship between SP and ESR. These findings suggest that SP might reflect somatic pain sensation to some extend and associate with the severity of inflammation. As we know, SP along with other neuropeptides can stimulate the release of inflammatory mediators such as IL-1, IL-6, IL-8, and TNF-α from both blood monocytes as well as fibroblast-like synoviocyte (FLS) in human body
[36–38]. Moreover, SP may favor the generation of memory Th17 cells by inducing IL-1β, IL-23, TNF-like 1A expression by monocytes
. These mediators on the one hand could act as chemoattractant molecule for further leucocyte migration. On the other hand, they might also directly bring about inflammatory response of the target cells through corresponding receptors and up-regulate the production of PGE2 from inflammatory cells which will advance the inflammation and pain
In our study, NK-1R, the specific receptors of SP, revealed strong and visible immune-staining tendency in synovial tissue from varied stages of DDH group. Previous studies have proved that inflammatory reactions in response to an immune irritation are strengthened in neuropathic animals and are partly mediated by NK-1R
[41–43]. Therefore, in this study, the up-regulated expression of NK-1R probably reflected a feedback, inducing series of intracellular signaling mechanisms to fit the negative stimuli outside. Also, researches demonstrated the validity of NK-1R antagonists in relieving cutaneous orofacial inflammatory pain and reducing hyperalgesia and cartilage destruction in the inflammatory joint in rats with adjuvant-induced arthritis
[44, 45]. Herein, we might hold the hypothesis that NK-1R antagonists could have therapeutic value in the treatment of pathological changes and the relief of arthritis evolvement in patients with DDH.
We know that SP stems from both neuronal and non-neuronal cells such as fibroblasts and some immune cells within the synovial tissue. According to the comparisons from tissue ELISA [Figure
1B], we speculate that SP in synovial tissue might mostly derived from segregation of peripheral free nerve endings, which coincided with that of previous research
[46, 47]. As neuropeptides were mainly secreted from DRG and transmitted through peripheral free nerve fibers, our findings indicated that more nerve fibers might invade into synovial tissue with the progress from DDH to DDH&OA, which probably involved in the upgrading of inflammation and pain sensation.
Several limitations also existed in this study. Firstly, it is impossible to obtain perfectly normal synovial specimens according to medical ethics requirement. Secondly, the age of patients in these groups was as close as possible. In our research, the mean age of DDH&OA group was 40.4 years, while the average age of patients with DDH was 28.3 years. We know that SP levels in tissue could change with ages
[48, 49]. Hence, doubtlessly, age differences between groups could affect the results. However, previous research has proved that SP levels in both animals and human may decrease with age
[50, 51]. In our study, patients in group of DDH&OA who were older than group of DDH represented higher levels of SP in both serum and tissue, which further certified that SP levels increase conspicuously in DDH&OA group compared to DDH group.